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Redefining fundamental concepts of transcription initiation in bacteria

Abstract

Despite enormous progress in understanding the fundamentals of bacterial gene regulation, our knowledge remains limited when compared with the number of bacterial genomes and regulatory systems to be discovered. Derived from a small number of initial studies, classic definitions for concepts of gene regulation have evolved as the number of characterized promoters has increased. Together with discoveries made using new technologies, this knowledge has led to revised generalizations and principles. In this Expert Recommendation, we suggest precise, updated definitions that support a logical, consistent conceptual framework of bacterial gene regulation, focusing on transcription initiation. The resulting concepts can be formalized by ontologies for computational modelling, laying the foundation for improved bioinformatics tools, knowledge-based resources and scientific communication. Thus, this work will help researchers construct better predictive models, with different formalisms, that will be useful in engineering, synthetic biology, microbiology and genetics.

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Fig. 1: Schematics of bacterial transcription initiation.
Fig. 2: Eσ intrinsic recognition by a sequence is neither necessary nor sufficient for that sequence to be a promoter.
Fig. 3: Different σ factors that start transcription at the same TSS define different promoters.
Fig. 4: Number of transcription factor binding sites without functional assignment versus number of transcription factor regulatory sites in Escherichia coli.
Fig. 5: Cis-regulatory architecture of the promoter deoCp2.
Fig. 6: Transcription unit and operon schematic.
Fig. 7: Schematic of signal and effector.

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Acknowledgements

C.M.-A. is a doctoral student from the Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), and has received CONACyT fellowship 576333. J.C.-V. acknowledges funding by Universidad Nacional Autónoma de México (UNAM) and the National Institutes of Health (5R01GM110597-04, 1RO1GM131643-01A1 and R01GM077678). J.C.-V. acknowledges being on sabbatical leave at the Center for Genomic Regulation, Barcelona, Spain. B.O.P. acknowledges the support of the Galletti Endowment at UC San Diego. The authors acknowledge J. Soffer, S. Gama-Castro and H. Salgado for useful discussions, and D. W. Sant for updating the definitions in Sequence Ontology. The authors also acknowledge the highly valuable suggestions from the referees.

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C.M.-A. researched the literature. C.M.-A., S.J.W.B., J.T.W., J.v.H., A.P.A., G.D.S., K.E., B.O.P., J.E.G. and J.C.-V. provided substantial contributions to discussions of the content. C.M.-A., S.J.W.B., J.T.W., J.v.H., A.P.A., G.D.S. and J.C.-V. wrote the article. C.M.-A., S.J.W.B., J.T.W., J.v.H., A.P.A., G.D.S., K.E., B.O.P. and J.C.-V. reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Julio Collado-Vides.

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The authors declare no competing interests.

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Nature Reviews Genetics thanks A. S. Ribeiro and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

Basic Formal Ontology: https://basic-formal-ontology.org/

EcoCyc: https://ecocyc.org

RegulonDB: http://regulondb.ccg.unam.mx/

RegulonDB Gensor Unit Groups: http://regulondb.ccg.unam.mx/central_panel_menu/integrated_views_and_tools/gensor_unit_groups

Sequence Ontology: http://www.sequenceontology.org

Supplementary information

Glossary

Activators

Gene products that increase transcription, indicating that their function is to enhance promoter activity.

Repressors

Gene products that decrease transcription, indicating that their function is to hamper promoter activity.

Operator

A genetic entity adjacent to a group of genes that regulates their expression and is sensitive to a repressor.

Operon

A set of adjacent co-transcribed genes.

Motifs

Representations of a collection of binding sites that summarize the binding-site characteristics.

Transcriptional pausing

A process through which the RNA polymerase slows down transcription during elongation.

5′-Rapid amplification of cDNA ends

(5′-RACE). A method to amplify mRNA between a defined internal site and its initiation site.

Global regulators

Transcription factors that affect a large number of genes involved in many different functions.

DNA supercoiling

The writhe of DNA over the double-stranded axis.

Monocistronic operons

Operons that encode a single gene product.

Transcriptional read-through

Transcription that allows RNA polymerase to continue transcription beyond termination sites.

Stimulons

Sets of genes whose products are increased in response to a common environmental stimulus.

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Mejía-Almonte, C., Busby, S.J.W., Wade, J.T. et al. Redefining fundamental concepts of transcription initiation in bacteria. Nat Rev Genet 21, 699–714 (2020). https://doi.org/10.1038/s41576-020-0254-8

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